Previous studies from this laboratory have shown that the lymphocytes from over half of patients with chronic lymphocytic leukemia have markedly reduced or absent 5'-nucleotidase (5(N) activity in their membranes. Studies outlined in this application will investigate the clinical significance and mechanism underlying this phenomenon. Lymphocytes will be isolated from blood of patients with CLL and other disorders and their 5'N activity determined. A histochemical assay will be developed to evauate the enzyme's distribution within the cells of a given host. The enzyme will be purified, and an antibody prepared to see whether the 5'N negative patients are merely lacking the activity or also devoid of the enzyme protein in their lymphocytes. The relationship between 5'N activity and the ratio of B/T lymphocytes will be established. Studies on the relatives of patients whose lymphocytes lack 5'N activity are planned. The effect of therapy on the level of the enzyme will also be evaluated The proposed investigations will establish the pathogenesis and possible clinical significance of the heterogeneity of 5'N in chronic lymphocytic leukemia.